Transcription factors mediate the enzymatic disassembly of promoter-bound 7sk snrnp to locally recruit p-tefb for transcription elongation

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Abstract

The transition from transcription initiation into elongation is controlled by transcription factors, which recruit positive transcription elongation factor b (P-TEFb) to promoters to phosphorylate RNA polymerase II. A fraction of P-TEFb is recruited as part of the inhibitory 7SK small nuclear ribonucleoprotein particle (snRNP), which inactivates the kinase and prevents elongation. However, it is unclear how P-TEFb is captured from the promoter-bound 7SK snRNP to activate elongation. Here, we describe a mechanism by which transcription factors mediate the enzymatic release of P-TEFb from the 7SK snRNP at promoters to trigger activation in a gene-specific manner. We demonstrate that Tat recruits PPM1G/PP2Cγ to locally disassemble P-TEFb from the 7SK snRNP at the HIV promoter via dephosphorylation of the kinase T loop. Similar to Tat, nuclear factor (NF)-κB recruits PPM1G in a stimulus-dependent manner to activate elongation at inflammatory-responsive genes. Recruitment of PPM1G to promoter-assembled 7SK snRNP provides a paradigm for rapid gene activation through transcriptional pause release.

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McNamara, R. P., McCann, J. L., Gudipaty, S. A., & D’Orso, I. (2013). Transcription factors mediate the enzymatic disassembly of promoter-bound 7sk snrnp to locally recruit p-tefb for transcription elongation. Cell Reports, 5(5), 1256–1268. https://doi.org/10.1016/j.celrep.2013.11.003

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